1. Technical Field
The present disclosure relates to compositions and formulations containing microparticles and to methods of processing such compositions and formulations.
2. Description of Related Technology
Microparticles, microspheres, and microcapsules, referred to herein collectively as “microparticles,” are solid or semi-solid particles having a diameter of less than one millimeter, more preferably less than 100 microns, which can be formed of a variety of materials, including but not limited to various polymers and proteins. Microparticles have been used in many different applications, primarily separations, diagnostics, and drug delivery.
The most well known examples of microparticles used in separations techniques are those which are formed of polymers of either synthetic or protein origin, such as polyacrylamide, hydroxyapatite, or agarose. These polymeric microparticles are commonly used to separate molecules such as proteins based on molecular weight and/or ionic charge, or by interaction with molecules chemically coupled to the microparticles.
In the diagnostic area, spherical beads or particles have been commercially available as a tool for biochemists for many years. For example, microparticles have been derivatized with an enzyme, a substrate for an enzyme, or a labeled antibody, and then interacted with a molecule to be detected, either directly or indirectly. A number of derivatized beads are commercially available with various constituents and sizes.
In the controlled drug delivery area, molecules have been encapsulated within microparticles or incorporated into a matrix to provide controlled release of the molecules. A number of different techniques have been used to make such microparticles from various polymers including phase separation, solvent evaporation, emulsification, and spray drying. Generally, the polymers form the supporting structure of the microparticles, and the drug or molecule of interest is incorporated into the supporting structure. Exemplary polymers used for the formation of microparticles include homopolymers and copolymers of lactic acid and glycolic acid (PLGA), block copolymers, and polyphosphazenes.
U.S. Patent Publication No. 2005/0170005 (the '005 publication) discloses phase separation methods for forming microparticles involving dissolving an active agent in an aqueous and/or aqueous-miscible solvent(s) containing a dissolved phase-separation enhancing agent(s) to form a solution in a single liquid phase. The solution is then subjected to a liquid-solid phase separation to cause the active agent to form solid spherical small particles (i.e., the solid phase) while the phase-separation enhancing agent(s) and solvent(s) comprise the liquid phase. The '005 publication discloses methods of harvesting microparticles including washing solutions and/or dry powders comprising microparticles with liquid media in which the active agent is insoluble and the undesired phase-separation enhancing agent is soluble. Disclosed liquid media include organic solvents and supercritical fluids. Such media can undesirably cause damage to any active agents, particularly proteins such as antibodies, within the microparticles.
The '005 publication further teaches that washing microparticles comprising proteins, such as insulin and hGH, with a liquid medium comprising an aqueous solution containing divalent cations, such as Zn2+, causes the protein to form a complex having decreased solubility. The solubility of microparticles comprising such proteins is sufficiently low in the divalent cation solution, but undesirable agglomeration of the particles is frequently observed when such solutions are used to wash the microparticles (as a result of complex formation).